Vacuum chamber for ion manipulation device

ABSTRACT

An ion manipulation method and device is disclosed. The device includes a pair of substantially parallel surfaces. An array of inner electrodes is contained within, and extends substantially along the length of, each parallel surface. The device includes a first outer array of electrodes and a second outer array of electrodes. Each outer array of electrodes is positioned on either side of the inner electrodes, and is contained within and extends substantially along the length of each parallel surface. A DC voltage is applied to the first and second outer array of electrodes. A RF voltage, with a superimposed electric field, is applied to the inner electrodes by applying the DC voltages to each electrode. Ions either move between the parallel surfaces within an ion confinement area or along paths in the direction of the electric field, or can be trapped in the ion confinement area. A predetermined number of pairs of surfaces are disposed in one or more chambers, forming a multiple-layer ion mobility cyclotron device.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No.14/146,922, filed Jan. 3, 2014, which claims the benefit of U.S.Provisional Application Ser. No. 61/809,660, filed Apr. 8, 2013, andboth are incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

The invention was made with Government support under ContractDE-AC05-76RLO1830, awarded by the U.S. Department of Energy. TheGovernment has certain rights in the invention.

TECHNICAL FIELD

This invention relates to ion manipulations in gases. More specifically,this invention relates to the use of RF and/or DC fields to manipulateions through electrodes, and building complex sequences of suchmanipulations in devices that include one or more such surfaces andstructures built upon the surfaces.

BACKGROUND OF THE INVENTION

As the roles for mass spectrometry and other technologies that involvethe use, manipulation or analysis of ions continue to expand, newopportunities can become limited by approaches currently used forextended sequences of ion manipulations, including their transportthrough regions of elevated pressure, reaction (both ion-molecule andion-ion), and ion mobility separations. As such manipulations becomemore sophisticated, conventional instrument designs and ion opticapproaches become increasingly impractical, expensive and/orinefficient.

SUMMARY OF THE INVENTION

The present invention is directed to devices and methods of manipulatingions in gases. In one embodiment, an ion manipulation device isdisclosed that is essentially lossless and allows extended sequences ofion manipulations. The device includes a pair of surfaces and in which apseudopotential is formed that inhibits charged particles fromapproaching either of the surfaces, and the simultaneous application ofDC potentials to control and restrict movement of ions between thesurfaces.

In one implementation this involves two substantially or identicalsurfaces that have an inner array of electrodes, surrounded by a firstouter array of electrodes and a second outer array of electrodes. Eachouter array of electrodes is positioned on either side of the innerelectrodes and contained within—and extending substantially along thelength of—each parallel surface in a fashion similar to the inner arrayof electrodes. The DC potentials are applied to the first and secondouter array of electrodes. The RF potentials, with a superimposedelectric field, are applied to the array of inner electrodes.

The superimposed electric field may be a static or dynamic electricfield. The static electric field may be, but is not limited to, a DCgradient. The dynamic electric field may be, but is not limited to, atraveling wave.

In one embodiment, the electrode arrangements on the two surfaces areidentical, such that similar or identical voltages are applied to both.However, the exact arrangement of electrodes can differ, and the precisevoltages applied to the two facing surfaces can also differ.

The pair of surfaces may be substantially planar, substantially parallelor parallel, or not flat.

In one embodiment, the RF potentials are applied along with the DCpotentials on the first and second outer electrode arrays. In anotherembodiment, the RF potentials are applied to only one of the twosurfaces. In another embodiment, the RF potentials are applied to bothof the surfaces.

In one embodiment, the electric field in all or a portion of the devicemay be replaced with a gas flow to move ions in the direction of the gasflow.

In one embodiment, the RF on at least one inner electrode is out ofphase with its neighboring inner electrode. In one embodiment the RF oneach electrode is phase shifted with its neighboring inner electrode toform a repulsive pseudopotential. In one embodiment, the RF on eachelectrode is approximately 180 degrees out of phase with its neighboringinner electrode to form the pseudopotential.

In one embodiment, the array of inner electrodes comprises at least twoelectrodes on the pair of surfaces. In another embodiment, the firstouter array of electrodes and the second outer array of electrodes eachcomprise at least two electrodes on the pair of surfaces. The device caninclude insulating material or resistive material between theelectrodes.

The RF voltage applied to the electrodes is between 0.1 kHz and 50 MHz,the electric field is between 0 and 5000 volts/mm, and operatingpressures from less than 10⁻³ torr to approximately atmospheric pressureor higher.

In one embodiment, the electrodes are perpendicular to at least one ofthe surfaces. In an alternative embodiment, the electrodes are parallelto at least one of the surfaces. The electrodes may comprise a thinconductive layer on the surfaces.

In certain embodiments, the device comprises multiple pairs of surfacesand allows transfer of the ions through an aperture to move betweendifferent pairs of surfaces.

The electrodes on the pair of surfaces may form one or more differentconfigurations. These configurations include, but are not limited to,the following: a substantially T-shaped configuration, allowing ions tobe switched at a junction of the T-shaped configuration; a substantiallyY-shaped configuration, allowing ions to be switched at a junction ofthe Y-shaped configuration; a substantially X-shaped or cross-shapedconfiguration, allowing ions to be switched at a junction of one or moresides of the X-shaped or cross-shaped configuration; and/or asubstantially multidirectional shape, such as an asterisk (*)—shapedconfiguration, with multiple junction points, allowing ions to beswitched at a junction to one or more sides of the configuration.

In one embodiment, the electric field allows the ions to move in acircular-shaped path, rectangular-shaped path, or other irregular path,to allow the ions to make more than one transit and, as one example,achieve higher resolution ion mobility separations.

The space between the surfaces may be filled with an inert gas or a gasthat ions react with ions.

Stacks of cyclotron stages may be used with the device to, for example,allow different ranges of ion mobilities to be separated in differentcyclotron stages, and in sum cover the entire range of ions in amixture.

The electric fields can be increased to cause ions to react ordissociate.

The device may be coupled to at least one of the following: a chargedetector, an optical detector, and/or a mass spectrometer.

In one embodiment, the device can be fabricated and assembled usingprinted circuit board technology and interfaced with a massspectrometer.

The device can be used to perform ion mobility separations and/ordifferential ion mobility separations (e.g., FAIMS).

Ions may be formed outside or inside the device using photoionization,Corona discharge, laser ionization, electron impact, field ionization,electrospray, or any other ionization technique that generates ions tobe used with the device.

In another embodiment of the present invention, an ion manipulationdevice is disclosed. The device includes a pair of substantiallyparallel surfaces. The device further includes an array of innerelectrodes contained within, and extending substantially along thelength of, each parallel surface. The device also includes a first outerarray of electrodes and a second outer array of electrodes, eachpositioned on either side of the inner electrodes, contained within, andextending substantially along the length of, each parallel surface,wherein a pseudopotential is formed that inhibits charged particles fromapproaching either of the parallel surfaces. The device also includes aRF voltage source and DC voltage sources, wherein a first DC voltagesource is applied to the first and second outer array of electrodes andwherein a RF frequency, with a superimposed electric field, is appliedto the inner electrodes by applying a second DC voltage to eachelectrode, such that ions move between the parallel surfaces within anion confinement area in the direction of the electric field or can betrapped in the ion confinement area.

In one embodiment, the RF frequency applied to the electrodes is between0.1 kHz and 50 MHz. The RF peak-to-peak voltage is approximately 10 to2000 volts. The electric field is between about 0 and about 5000volts/mm, and the pressure is between 10⁻³ torr and atmosphericpressure.

In one embodiment, one or more of the electrodes has 0.5 to 10 mm relieffrom the surface, so that degradation of device performance due tocharging of the surfaces between electrodes is prevented.

In another embodiment of the present invention, a method of manipulatingions is disclosed. The method includes injecting ions between a pair ofsubstantially parallel surfaces, wherein each pair of parallel surfacescontains an array of inner electrodes and a first and second array ofouter electrodes on either side of the inner electrodes. The methodfurther includes applying RF fields to confine the ions between thesurfaces. The method also includes applying a first DC field to theouter electrodes equal to or higher than a second DC field applied tothe inner electrodes to confine ions laterally. The method also includessuperimposing the second DC field on the RF field to further confine andmove the ions along in a direction set by the electric field.

In one embodiment, the method further includes transferring the ionsthrough an aperture in at least one of the pairs of parallel surfaces,wherein the ions travel to between another pair of parallel surfaces.

In another embodiment of the present invention, an ion manipulationdevice is disclosed. The device includes multiple pairs of substantiallyparallel surfaces. The device further includes an array of innerelectrodes contained within, and extending substantially along thelength of, each parallel surface. The device also includes a pluralityof outer arrays of electrodes, wherein at least one outer array ofelectrodes is positioned on either side of the inner electrodes. Eachouter array is contained within and extends substantially along thelength of each parallel surface, forming a potential that can inhibitions moving in the direction of the outer array of electrodes, and whichworks in conjunction with a pseudopotential created by potentialsapplied to the inner array of electrodes that inhibits charged particlesfrom approaching either of the parallel surfaces. The device alsoincludes a RF voltage source and a DC voltage source. A DC voltage isapplied to the plurality of outer arrays of electrodes. The RF voltage,with a DC superimposed electric field, is applied to the innerelectrodes by applying the DC voltage to each electrode, such that ionswill move between the parallel surfaces within an ion confinement areain the direction of the electric field or have their motion confined toa specific area such that they are trapped in the ion confinement area.Transfer of the ions to another pair of parallel surfaces or throughmultiple pairs of parallel surfaces is allowed through an aperture inone or more of the surfaces.

In another embodiment of the present invention, the electrodes havesignificant relief from the surfaces. Regions of such relief can be usedto alter the electric fields, or also to prevent effects due to chargingof nonconductive regions between electrodes. Such designs haveparticular value in regions where ion confinement is imperfect, such asin reaction regions where ion-molecule or ion-ion reactions result inion products that have m/z values either too high or too low foreffective ion confinement. In such cases just the reaction regions mayrequire electrodes that extend from the surfaces, and in such casesthese regions may have different, often larger, spacing between the twosurfaces.

In another embodiment of the present invention RF potentials having twoor more distinct frequencies and different electric fields areco-applied to the arrays of electrodes on the two surfaces and with apattern of application that creates a pseudopotential that inhibitscharged particles from approaching one or both of the substantiallyparallel surfaces over a substantially greater m/z range than would befeasible with RF potentials of a single frequency.

In another embodiment of the present invention, each central or innerelectrode is replaced by two or more electrodes with adjacent electrodeshaving different phase of the RF applied such that the traps formed forions close to one of the surfaces are substantially reduced, resultingin improved performance such as a reduction of possible trapping effectsor reduction in the m/z range that can be transmitted, particularly whenion currents near the upper limit are being transmitted.

In another embodiment of the present invention, a vacuum chamberassembly for ion manipulation devices is disclosed. The chamber assemblyincludes multiple pairs of substantially parallel surfaces. Arrays ofelectrodes are coupled to the surfaces to which RF potentials areapplied to at least one of the surfaces in order to create apseudopotential that inhibits charged particles from approaching thesurfaces. The chamber assembly includes the simultaneous application ofDC potentials to control and restrict movement of ions in between eachpair of surfaces. A predetermined number of pairs of surfaces aredisposed in a chamber to form a multiple-layer ion mobility cyclotrondevice.

In one embodiment, the vacuum chamber assembly includes a plurality ofchambers arranged in a stack, wherein the predetermined number of pairsof surfaces are disposed in each chamber.

In one embodiment, brackets are used at different locations to providethe solid structure of the stacked chambers, and also to hermeticallypress a seal member on the top and the bottom of each chamber.

The chamber assembly can further include a first insulation platebetween each ion mobility device inside of the chamber, and a secondinsulation plate between chamber.

The first insulation plate is made of, but not limited to, one of thefollowing: ceramic, Teflon, fiberglass, polyether ether ketone (PEEK),or polycarbonate.

The second insulation plate is made of, but not limited to, a metalflame with an embedded nonconductive plate. The embedded nonconductiveplate is, but not limited to, ceramic, Teflon, fiberglass, PEEK, orpolycarbonate.

The chamber assembly can further include a top cover or a firstintermediary plate located above a top ion mobility device in thechamber, and a bottom cover or a second intermediary plate located belowa bottom ion mobility device in the chamber.

The top cover may include bolt holes for sealing purposes. The bottomcover may include a metal plate and an insulation plate embedded on themetal plate. The metal plate may include sealing surfaces that attach toa bottom opening of each chamber to maintain the vacuum.

In one embodiment, each of the first and second intermediary platesincludes a metal plate and an insulation plate embedded on the metalplate. The metal plate includes sealing surfaces that attach to anopening of each chamber to maintain the vacuum.

In one embodiment, the chamber assembly further includes a side lid withelectrical feedthrough interfaces. The side lid may be made of anonconductive material.

In one embodiment, an inlet of each chamber is coupled to an ion sourceand an outlet of each chamber is coupled to a mass spectrometer. The ionsource may be, but is not limited to, an ion funnel or a dual ionfunnel.

In one embodiment, each chamber includes a maximum of ten ion mobilitycyclotron devices.

In one embodiment, the height of each chamber is between two and teninches.

The chambers may be stacked with a vacuum seal applied to a matingsurface of an adjacent chamber.

In another embodiment of the present invention, a vacuum chamber stackfor ion manipulation devices is disclosed. The chamber includes multiplepairs of substantially parallel surfaces in each chamber. Arrays ofelectrodes are coupled to the surfaces to which RF potentials areapplied to at least one of the surfaces in order to create apseuodopotential that inhibits charged particles from approaching thesurfaces. The chamber includes simultaneous application of DC potentialsto control and restrict movement of ions in between each pair ofsurfaces. A plurality of vacuum chambers are arranged in a stack,wherein a predetermined number of pairs of surfaces are disposed in eachchamber to form a multiple-layer ion mobility cyclotron device. Thechamber further includes a plurality of brackets between each chamber.The chamber also includes a first insulation plate between each ionmobility device inside of each chamber, and a second insulation platebetween each chamber.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic of a portion of an individual parallel surfacecontaining an arrangement of electrodes for an ion manipulation device,in accordance with one embodiment of the present invention.

FIG. 1B is a schematic of a portion of an ion manipulation device, inaccordance with one embodiment of the present invention.

FIG. 2 is a schematic of a portion of an individual parallel surfacecontaining an arrangement of electrodes, and also showing an ionconfinement area, for an ion manipulation device, in accordance with oneembodiment of the present invention.

FIG. 3A is a schematic of an individual parallel surface containing anarrangement of electrodes for an ion manipulation device, in accordancewith one embodiment of the present invention.

FIG. 3B is a schematic of an ion manipulation device, in accordance withone embodiment of the present invention.

FIG. 4A is a schematic of an ion manipulation device, in accordance withone embodiment of the present invention.

FIG. 4B shows where the ions will be confined when DC and RF potentialsare applied to the device of FIG. 4A, in accordance with one embodimentof the present invention.

FIGS. 5A, 5B, and 5C show simulations for an ion switch in a T-shapedconfiguration of an ion manipulation device, in accordance with oneembodiment of the present invention.

FIG. 6 shows dual polarity trapping regions for ion-ion reactions in anion manipulation device, in accordance with one embodiment of thepresent invention.

FIG. 7 shows simulations of an ion switch in an “elevator” configurationwhere ions are transferred through one or more apertures to move betweendifferent pairs of parallel surfaces in an ion manipulation device, inaccordance with one embodiment of the present invention.

FIG. 8 shows simulations of an ion switch in an “elevator” configurationhaving multiple levels where ions are transferred through one or moreapertures to move between different pairs of parallel surfaces in an ionmanipulation device, in accordance with one embodiment of the presentinvention.

FIG. 9 shows an ion manipulation device implemented as an ion mobilitycyclotron for high resolution separations, in accordance with oneembodiment of the present invention.

FIG. 10 shows an ion mobility device coupled between an array of ionsources and an array of mass spectrometer devices, in accordance withone embodiment of the present invention.

FIG. 11 shows a plurality of vacuum chambers arranged in stack forhousing one or more ion manipulation devices, in accordance with oneembodiment of the present invention.

FIG. 12 shows examples of insulation plates disposed within or betweenthe chambers of FIG. 11.

FIG. 13 shows one example of brackets at different locations to providethe solid structure of the stacked chambers of FIG. 11 and also tohermetically press a seal member on the top and bottom of each chamber.

FIG. 14 shows two of a plurality of chambers containing, in thisexample, five layers of ion manipulation devices with insulation platesinstalled between each layer for electrical insulation purposes, inaccordance with one embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is directed to devices, apparatuses, and method ofmanipulating ions. The present invention uses electric fields to createfield-defined pathways, traps, and switches to manipulate ions in thegas phase, and with minimal or no losses. Embodiments of the deviceenable complex sequences of ion separations, transfers, path switching,and trapping to occur in the space between two surfaces positioned apartand each patterned with conductive electrodes. In one embodiment, thepresent invention uses the inhomogeneous electric fields created byarrays of closely spaced electrodes to which readily generatedpeak-to-peak RF voltages (V_(p-p)˜100 V; ˜1 MHz) are applied withopposite polarity on adjacent electrodes to create effective potentialor pseudopotential fields that prevent ions from approaching thesurfaces. These ion confining fields result from the combination of RFand DC potentials, with the RF potentials among other roles creating apseudopotential that prevents loss of ions and charged particles overcertain m/z ranges to a surface, and the DC potentials among other rolesbeing used to confine ions to particular defined paths of regionsbetween the two surfaces, or to move ions parallel to the surfaces. Theconfinement functions over a range of pressures (<0.001 torr to ˜1000torr), and over a useful, broad, and adjustable mass to charge (m/z)range. Of particular interest is the ability to manipulate ions that canbe analyzed by mass spectrometers, and where pressures of <0.1 to ˜50torr can be used to readily manipulate ions over a useful m/z range,e.g., m/z 20 to >5,000. This effective potential works in conjunctionwith DC potentials applied to side electrodes to prevent ion losses, andallows the creation of ion traps and/or conduits in the gap between thetwo surfaces for the effectively lossless storage and/or movement ofions as a result of any gradient in the applied DC fields.

In one embodiment, the invention discloses the use of RF and DC fieldsto manipulate ions. The manipulation includes, but is not limited to,controlling the ion paths, separating ions, reacting ions, as well astrapping and accumulating the ions by the addition of ions to thetrapping region(s). The ion manipulation device, which may be referredto as an “ion conveyor” or Structure for Lossless Ion Manipulation(SLIM), uses arrays of electrodes on substantially parallel surfaces tocontrol ion motion. Combinations of RF and DC potentials are applied tothe electrodes to create paths for ion transfer and ion trapping. Theparallel surfaces may be fabricated using, but not limited to, printedcircuit board technologies or 3D printing.

FIG. 1A is a schematic of a portion of an individual parallel surface100 containing a first and second array of outer electrodes 120 and anarray of inner electrodes 130 for an ion manipulation device, inaccordance with one embodiment of the present invention. The array ofinner electrodes 130 is contained within and extends substantially alongthe length of the surface 100. The array of outer electrodes 120,positioned on either side of the inner electrodes 130, is also containedwithin and extends substantially along the length of the surface 100.

FIG. 1B is a schematic of a portion of an ion manipulation device 200,in accordance with one embodiment of the present invention. The device200 includes a pair of substantially parallel surfaces 210 and 215. Eachsurface contains an array of inner electrodes 230 and a first and secondarray of outer electrodes 220. The arrays of outer electrodes 220 arepositioned on either side of the array of inner electrodes 230. Thearrays of electrodes 220 and 230 are contained within and extendsubstantially along the length of each parallel surface 210 and 215. Thearrangement of electrodes on the opposing surfaces can be identical aswell as the electric field applied. Alternately, either the detailedelectrode arrangements or the electric fields applied can be differentin order to affect ion motion and trapping between the device.

The portion of the device 200 also includes a RF voltage source and DCvoltage sources (not shown). In one embodiment, the DC voltages areapplied to the first and second outer array of electrodes 220. The RFvoltage, of opposite polarity upon adjacent electrodes, with asuperimposed DC electric field, is applied to the inner array ofelectrodes 220. In the arrangement of FIG. 2, with the RF and DC fieldsapplied as such, ions either move between the parallel surfaces 210 and215 within an ion confinement area in the direction of the electricfield or can be trapped in the ion confinement area depending on the DCvoltages applied.

In one embodiment, the RF on at least one inner electrode is out ofphase with its neighboring inner electrode. In another embodiment, eachinner electrode is 180 degrees out of phase with its neighboring innerelectrode to form a pseudopotential that inhibits charged particles fromapproaching either of the parallel surfaces. In another embodiment eachinner electrode is replaced by two or more electrodes to which RF isapplied to each and with one or more the electrodes being out of phasewith its neighboring inner electrodes.

The electric field also allows the ions to move in a circular-shaped ora rectangular-shaped path, to allow the ions to make more than onetransit. Stacks of cyclotron stages can be used with the device 200.Arrangements with cyclotrons, where the ions traverse a circular path,will allow very high-resolution mobility separations with small physicalsize.

In one embodiment, the array of inner electrodes 220 comprises at leasttwo electrodes on the pair of parallel surfaces 210 and 215. The firstouter array of electrodes and the second outer array of electrodes 220may each comprise at least two electrodes on the pair of parallelsurfaces 210 and 215.

In one embodiment the RF is simultaneously applied with DC potentials tothe electrodes 220, and in another embodiment the RF applied to adjacentouter electrodes has opposite polarity.

In one embodiment the space between the surfaces 210 and 215 may includea gas or otherwise vaporized or dispersed species that ions react with.

In one embodiment the electrodes 220 are augmented by an additional setof electrodes further displaced from the central electrodes that has DCpotentials applied that are opposite in polarity to allow theconfinement or separation of ions of opposite polarity.

The device 200 can be coupled to other devices, apparatuses and systems.These include, but are not limited to, a charge detector, an opticaldetector, and/or a mass spectrometer. The ion mobility separationpossible with the device 200 can be used for enrichment, selection,collection and accumulation over multiple separations of any mobilityresolved species.

The device 200 may be used to perform ion mobility separations.

In one embodiment, the RF frequency applied to the electrodes 230 isbetween 0.1 kHz and 50 MHz, and the electric field is between 0 and 5000volts/mm.

In one embodiment, the electrodes 220 and 230 are perpendicular to atleast one of the surfaces and may comprise a thin conductive layer onthe surfaces 210 and 215.

The device 200 can include multiple pairs of substantially parallelsurfaces, allowing transfer of the ions through an aperture to movebetween different pairs of parallel surfaces.

The electrodes on the pair of surfaces 210 and 215 can form one of manydifferent configurations. In one embodiment, the surfaces 210 and 215form a substantially T-shaped configuration, allowing ions to beswitched at a junction of the T-shaped configuration. In anotherembodiment, the surfaces 210 and 215 form a substantially Y-shapedconfiguration, allowing ions to be switched at a junction of theY-shaped configuration. In another embodiment, the surfaces 210 and 215form a substantially X-shaped or cross-shaped configuration, allowingions to be switched at a junction or one or more sides of the X-shapedconfiguration. In another embodiment, the surfaces 210 and 215 form asubstantially multidirectional shape, such as an asterisk (*)-shapedconfiguration, with multiple junction points, allowing ions to beswitched at a junction to one or more sides of the configuration.Devices may be constituted from any number of such elements.

The electrodes on the surfaces can have any shape, not being limited tothe rectangular shapes such as in FIG. 1. For example, the electrodescan be round, have ellipse or oval shapes, or be rectangles with roundedcorners.

FIG. 2 is a schematic of an individual parallel surface 300 containingan arrangement of electrodes 320 and 330 with an ion confinement area340 for an ion manipulation device, in accordance with one embodiment ofthe present invention. Static DC voltages may be applied to the outerelectrodes 320 with RF applied to the inner electrodes 330. Each centralelectrode can have RF applied out of phase with its neighboringelectrode.

A DC or other electric field is superimposed on the RF and applied tothe inner electrodes 330 to move ions through the device of FIG. 2, inaddition to successively lower voltages applied on each outer electrode320—moving from left to right or alternatively from right to left,depending on the polarity and the desired direction of motion. Thiselectric field forces ions to the right, while the RF and DC fields alsoconfine ions to a central region of the device as shown. Voltagepolarities can be changed to allow manipulation of both negative andpositive ions.

FIG. 3A is a schematic of an individual parallel surface 400 containingan arrangement of electrodes for an ion manipulation device, inaccordance with one embodiment of the present invention. The surface 400includes electrodes 450 that are individually programmable by a DCvoltage, electrodes 430 associated with a negative RF voltage, andelectrodes 435 associated with a positive RF voltage—where negative andpositive RF refers to the phase of the RF waveform.

FIG. 3B is a schematic of an ion manipulation device 500, in accordancewith one embodiment of the present invention. The ion manipulationdevice 500 includes substantially parallel surfaces 510 and 515 that aresimilar to the surface 400 of FIG. 3A. The device 500 includeselectrodes 550 that are individually programmable by a DC voltage,electrodes 530 associated with a negative RF voltage, and electrodes 535associated with a positive RF voltage. In this arrangement, ions areconfined between the surfaces 510 and 515. The ions move in thedirection defined by an electric field.

FIG. 4A is a schematic of an ion manipulation device, in accordance withone embodiment of the present invention. The central or inner electrodeshave RF fields applied with opposite polarity to adjacent electrodes tocreate fields that prevent ions from closely approaching the surfaces.Ions are moved according to their mobilities under DC fields applied tothe outer electrodes.

FIG. 4B shows the trapping volume of ions between the surfacescontaining electrodes of an ion manipulation device, in accordance withone embodiment of the present invention. Both positive and negativecharged ion particles are confined in overlapping areas of the ionmanipulation device. This can be accomplished using multiple arrays ofouter electrodes and applying both RF and DC potentials.

The devices of the present invention provide for at least the following:lossless (a) linear ion transport and mobility separation, (b) iontransport around a corner (e.g., a 90 degree bend), (c) ion switches todirect ions to one of at least two paths, (d) ion elevators fortransporting ions between different levels of multilevel ionmanipulation devices, (e) ion traps for trapping, accumulation, andreaction of ions of one polarity. These devices can be combined tocreate a core module for more complex ion manipulation devices such asan ion mobility cyclotron. In one implementation, integrating severalmodules will allow fabrication of a single level device that will enablethe separation of ions over periods on the order of 0.1 to 10 secondswhile achieving resolutions of up to approximately 1000 for species overa limited range of mobilities. The range of mobilities, and thefractions of the total biomolecule ion mixture that can be separated,decreases as the resolution is increased. Thus, an ion mobilitycyclotron module can provide a useful and targeted separation/analysiscapability—where information is desired for a limited subset of species.

The integrated device can consist of a stack of modules each covering adifferent portion of the full mobility spectrum. In combination, theyprovide separations that cover the full range of ion mobilities neededfor a sample, while at the same time making efficient use of all theions from the sample. The integrated device can draw upon the ionswitch, elevator, and trap components to provide a low resolutionseparation that partitions ions from the sample into fractions that aredelivered to different cyclotrons using the ion elevator.

FIGS. 5A, 5B, and 5C show simulations of an ion switch in a T-shapedconfiguration of an ion manipulation device, in accordance with oneembodiment of the present invention. These ion paths can be controlledusing switch elements. As shown in FIGS. 5A, 5B, and 5C, the ion pathcan be dynamically or statically changed by modifying the electrodearrangement of the device and/or varying the RF and DC voltages. Theions can be switched at a junction as shown in FIG. 5A, move in astraight path as shown in FIG. 5B, and/or curve or bend around a cornerat the junction as shown in FIG. 5C. Alternatively, the pair of parallelsurfaces of the device can form other configurations such as, but notlimited to, Y-shaped configurations, X-shaped or cross-shapedconfigurations, and other multidirectional shapes.

FIG. 6 shows dual polarity trapping regions for ion-ion reactions in anion manipulation device, in accordance with one embodiment of thepresent invention. Different polarity of ions, positive and negative,can be trapped at the same time in at least partially overlappingphysical volumes between the two surfaces of the device using multiplesets of electrodes and applying both RF and DC potentials. Additional RFor DC potentials can be applied to heat and excite either the positiveor negatively charged ions in order to change the reaction rate orreaction products.

FIG. 7 shows simulations of an ion switch in an “elevator” configurationwhere ions are transferred through one or more apertures to move betweendifferent pairs of parallel surfaces in an ion manipulation device, inaccordance with one embodiment of the present invention. This allowsmulti-dimensional ion manipulation using the ion manipulation device. Insome embodiments additional electrodes are added to increase theefficiency of transfer between different levels, including electrodeswith DC and/or RF potentials with different polarities on adjacentelectrodes.

FIG. 8 shows simulations of an ion switch in an “elevator” configurationhaving multiple levels where ions are transferred through one or moreapertures to move between different pairs of parallel surfaces in an ionmanipulation device, in accordance with one embodiment of the presentinvention.

FIG. 9 is a schematic showing an ion manipulation device implemented asan ion mobility cyclotron. Ions entering from the ion source areinitially trapped before a first low resolution separation. Separatedions of interest are trapped and then injected for cyclotronseparations, potentially achieving resolutions greater than 1000. Theswitching points direct ions to one of at least two paths. All fourpoints—the switching points and the bends—are where changes in therotating DC electric field can be applied to create the cyclotronmotions.

FIG. 10 shows an ion mobility device coupled between an array of ionsources and an array of mass spectrometer devices, in accordance withone embodiment of the present invention. As shown in FIG. 10, thepresent invention also enables multiplexed sample analyses using anarray of ion sources and multiple ion separations in parallel—separatedduring travel through the device—and detected using an array of highspeed, high dynamic range time-of-flight (TOF) mass spectrometers (MS).

FIG. 11 shows a plurality of vacuum chambers 610 arranged in stack 600for housing one or more ion manipulation devices within each chamber610, in accordance with one embodiment of the present invention.Although six chambers are shown in FIG. 11, it should be noted that thestack 600 is not limited to any specific number of chambers.

The chambers 610 include at least one inlet 660 and at least one outlet.The inlet may be coupled to an ion source interface such as, but notlimited to, an ion funnel or a dual ion funnel 620. The outlet may becoupled to a mass spectrometer or analyzer 640 directly or indirectlyvia another ion device 630 for manipulating and/or focusing ions. In theembodiment of FIG. 11, the bottom chamber of the stack 600 is coupledthrough an ion funnel chamber 630 to the mass spectrometer 640 at theoutlet. In the inlet, two ion funnel chambers 620 are connected as theion source interface. One or more of the chambers 610 can include asensor 650 such as, but not limited to, a pressure sensor.

FIG. 12 shows examples of insulation plates 700 disposed within orbetween the chambers 610 of FIG. 11. The plates 700 include a firstinsulation plate 710, a second insulation plate 720, a top cover 730,and a bottom cover 740.

The first insulation plate 710 is coupled between individual ionmanipulation devices or cyclotron devices inside of the chamber. Thefirst plate 710 can be made of, but not limited to, ceramic, Teflon,fiberglass, PEEK, or polycarbonate. In one embodiment, the first plate710 is supported by standoffs at corners of the first plate 710.

The second insulation plate 720 is coupled between each chamber in astack of chambers. In one embodiment, the second plate 720 is made of ametal flame with an embedded nonconductive plate. The nonconductiveplate can be made of, but not limited to, ceramic, Teflon, fiberglass,PEEK, or polycarbonate.

The top cover 730 is located above a top ion mobility device in thechamber and includes bolt holes for sealing purposes. The bottom cover740 is located below a bottom ion mobility device in the chamber.

The bottom cover 740 includes a metal plate and an insulation plateembedded on the metal plate. The metal plate includes sealing surfacesthat attach to a bottom opening of each chamber in a stack to maintainthe vacuum.

FIG. 13 shows one example of brackets 770 at different locations toprovide the solid structure of the stacked chambers of FIG. 11 and alsoto hermetically press a seal member on the top and bottom of eachchamber.

FIG. 14 shows two 802 and 804 of a stack 800 of chambers containing, inthis example, five layers of ion manipulation devices 805 with firstinsulation plates 810 installed between each layer 805 for electricalinsulation purposes, in accordance with one embodiment of the presentinvention. As shown in FIG. 14, the chamber 802 (or 804) includes abottom cover 840, a top cover 830, and a second insulation plate 820disposed between chamber 802 and chamber 804. It should be noted thateach chamber 802 and 804 is not limited to five layers or ion devicesand can include between 1 and about 10 layers or ion devices.

EXAMPLE

The following examples serve to illustrate certain embodiments andaspects of the present invention and are not to be construed as limitingthe scope thereof

A device, as shown in FIG. 1B, was used to manipulate ions injected froman external ESI source. Simulations were performed to refine the designof the device; e.g. electrode sizes and spacing between the planarsurfaces were adjusted. Boards were fabricated with electrode regions totest capabilities that included efficient ion transportation, ionmobility separations, ion trapping, and ion switching betweenalternative corridors or paths.

In one test, ions were introduced from the external ESI source andinjected into one of the ion corridors at a pressure of ˜4 torr. RFfrequencies of approximately 1.4 MHz and 140 Vp-p were applied to createrepulsive fields to confine ions within the ion corridors between theopposing board surfaces. The RF fields were combined with DC for furtherconfinement to the corridors and also to move the ions along thecorridors based upon their ion mobilities. Separate electrodes were usedto measure ion currents at various locations and evaluate iontransmission efficiency through different areas of the device. Initialmeasurements showed that ions can be efficiently introduced into suchdevices, as well as transported through them with minimal losses.

The device of the present invention, including its various embodiments,can be manufactured at very low cost and is very flexible, allowingapplication to many different areas in mass spectrometry. As oneexample, the device can be fabricated and assembled using printedcircuit board technology and interfaced with a mass spectrometer. Thedevice can also be lossless. Ion mobility separation and complex ionmanipulation strategies can be easily implemented with the device.

The device of the present invention, including its various embodiments,can be altered in its performance by the use of electrodes that havesignificant thickness and thus substantial relief from one or both ofthe surfaces. The thickness can vary between electrodes, and individualelectrodes can have variable thickness. These electrodes can be used tocreate electric fields not practical for very thin electrodes (e.g.surface deposited such as on conventional printed circuit boards).Regions of devices with such electrodes have particular value whenincomplete or inefficient ion confinement may occur, such as for verylow or high m/z ions created by reactions that can provide awell-controlled electric field and prevent degraded performance fromdistorted electric fields due to the charging of surfaces betweenelectrodes.

Embodiments of the present invention can improve and extend analysiscapabilities in, for example, proteomics, metabolomics, lipidomics,glycomics, as well as their applications to a broad range of biologicaland chemical measurements and applicable research areas. Utilization ofthe ion manipulation device can lead to faster, cheaper, and moresensitive measurements relevant to understanding chemical,environmental, or biological systems. The present invention enablesMS-based approaches involving complex ion manipulations in the gas phasecapable of augmenting or completely displacing conventional liquid phaseapproaches. The present invention also enables separations and other ionmanipulations over extended periods in a nearly lossless fashion. Thesecapabilities lead to very fast and high resolution gas phase separationsof ions.

The present invention has been described in terms of specificembodiments incorporating details to facilitate the understanding of theprinciples of construction and operation of the invention. As such,references herein to specific embodiments and details thereof are notintended to limit the scope of the claims appended hereto. It will beapparent to those skilled in the art that modifications can be made inthe embodiments chosen for illustration without departing from thespirit and scope of the invention.

We claim:
 1. A vacuum chamber assembly for ion manipulation devicescomprising: a. multiple pairs of substantially parallel surfaces; b.arrays of electrodes coupled to the surfaces to which RF potentials areapplied to at least one of the surfaces in order to create apseudopotential that inhibits charged particles from approaching thesurfaces; and c. simultaneous application of DC potentials to controland restrict movement of ions in between each pair of surfaces; whereina predetermined number of pairs of surfaces are disposed in a chamber toform a multiple-layer ion mobility cyclotron device.
 2. The vacuumchamber assembly of claim 1 further comprising a first insulation platebetween each ion mobility device inside of the chamber.
 3. The vacuumchamber assembly of claim 2 further comprising a plurality of chambersarranged in a stack, wherein the predetermined number of pairs ofsurfaces are disposed in each chamber.
 4. The vacuum chamber assembly ofclaim 3 further comprising a plurality of brackets between each chamber.5. The vacuum chamber assembly of claim 4 further comprising a secondinsulation plate between each chamber.
 6. The vacuum chamber assembly ofclaim 5 wherein the first insulation plate is made of ceramic, Teflon,fiberglass, polyether ether ketone (PEEK), or polycarbonate.
 7. Thevacuum chamber assembly of claim 5 wherein the second insulation is madeof a metal flame with an embedded nonconductive plate, wherein theembedded nonconductive plate is ceramic, Teflon, fiberglass, PEEK, orpolycarbonate.
 8. The vacuum chamber assembly of claim 5 furthercomprising a top cover or a first intermediary plate located above a topion mobility device in the chamber, and a bottom cover or a secondintermediary plate located below a bottom ion mobility device in thechamber.
 9. The vacuum chamber assembly of claim 8 wherein the top coverincludes bolt holes for sealing purposes.
 10. The vacuum chamberassembly of claim 9 wherein the bottom cover includes a metal plate andan insulation plate embedded on the metal plate, wherein the metal plateincludes sealing surfaces that attach to a bottom opening of eachchamber to maintain the vacuum.
 11. The vacuum chamber assembly of claim9 wherein each of the first and second intermediary plates includes ametal plate and an insulation plate embedded on the metal plate, whereinthe metal plate includes sealing surfaces that attach to an opening ofeach chamber to maintain the vacuum.
 12. The vacuum chamber assembly ofclaim 11 further comprising a side lid with electrical feedthroughinterfaces, wherein the side lid is made of a nonconductive material.13. The vacuum chamber assembly of claim 1 wherein an inlet of eachchamber is coupled to an ion source and an outlet of each chamber iscoupled to a mass spectrometer.
 14. The vacuum chamber assembly of claim13 wherein the ion source is an ion funnel or a dual ion funnel.
 15. Thevacuum chamber assembly of claim 1 wherein each chamber includes amaximum of ten ion mobility cyclotron devices.
 16. The vacuum chamberassembly of claim 15 wherein the height of each chamber is between twoand ten inches.
 17. The vacuum chamber assembly of claim 16 wherein thechambers are stacked with a vacuum seal applied to a mating surface ofan adjacent chamber.
 18. A vacuum chamber stack for ion manipulationdevices comprising: a. multiple pairs of substantially parallel surfacesin each chamber; b. arrays of electrodes coupled to the surfaces towhich RF potentials are applied to at least one of the surfaces in orderto create a pseudopotential that inhibits charged particles fromapproaching the surfaces; and c. simultaneous application of DCpotentials to control and restrict movement of ions in between each pairof surfaces; d. a plurality of vacuum chambers arranged in a stack,wherein a predetermined number of pairs of surfaces are disposed in eachchamber to form a multiple-layer ion mobility cyclotron device; e. aplurality of brackets between each chamber; and f. a first insulationplate between each ion mobility device inside of each chamber, and asecond insulation plate between each chamber.